3.5 | Case Study: E194G of CASQ
The calsequestrin (CASQ) is the Ca2+ buffering protein, which could store large amounts of Ca2+ in the cardiac and skeletal muscles. Ca2+ is an essential molecular that could regulate diverse cellular processes, such as gene transcription, cell proliferation, or migration (Kim, Tam, Siems, & Kang, 2005; MacLennan, Abu-Abed, & Kang, 2002; Manno et al., 2017). Though most researches of CASQ are focus on the cardiac muscle, CASQ in the Ca2+ signal pathway is also vital in cancer research (Terentyev et al., 2003). It is reported that the Ca2+ signaling pathway is highly correlated to tumor growth or metastatic (Stewart, Yapa, & Monteith, 2015), and E194G of CASQ has been found in glioblastoma patients (Parsons et al., 2008). In CASQ, T189, E194, and D196 would form a pack harboring Ca2+ (Sanchez, Lewis, Danna, & Kang, 2012). Hence, this substitution, E194G, would lose it functional and destroy the Ca2+ binding (Figure 5).
Although no micro-environment descriptor has a significant difference at 95% confidence interval between the distribution of cancer-related and neutral SAVs in GLU altered to GLY sub-group, several relevant descriptors are found in the case of E194G in CASQ. E194 has higher WCN values of oxygen in a single SAV chain and atoms in other molecular due to CASQ is a GLU and ASP rich and Ca2+ buffering protein (Figure 6 a, b). Furthermore, for the micro-environment around E194, higher WCN values are found than the third quartile of cancer-related SAVs in H -polar (RKEDQN), V -medium (NVEQIL), Z -low polarizability(GASDT), P -high polarity (HQRKNED), F -acidic (DE), and E -acidic (DE) descriptors and lower than the first quartile in E -sulfur-containing (CM). The boxplot of the micro-environment descriptors in GLU altered to GLY sub-group is shown in figure 6.